Among Líĺwat people of the Interior Plateau of British Columbia, an oral tradition relays how early ancestors used to ascend Qẃelqẃelústen, or Mount Meager. The account maintains that those climbers could see the ocean, which is not the case today, because the mountain is surrounded by many other high peaks, and the Strait of Georgia is several mountain ridges to the west. However, the mountain is an active and volatile volcano, which last erupted circa 2360 cal BP. It is also the site of the largest landslide in Canadian history, which occurred in 2010. Given that it had been a high, glacier-capped mountain throughout the Holocene, much like other volcanoes along the coastal range, we surmise that a climber may have reasonably been afforded a view of the ocean from its prior heights. We conducted viewshed analyses of the potential mountain height prior to its eruption and determined that one could indeed view the ocean if the mountain were at least 950 m higher than it is today. This aligns with the oral tradition, indicating that it may be over 2,400 years old, and plausibly in the range of 4,000 to 9,000 years old when the mountain may have been at such a height.

Occurrence of cryptosporidiosis has been associated with weather conditions in many settings internationally. We explored statistical clusters of human cryptosporidiosis and their relationship with severe weather events in New Zealand (NZ). Notified cases of cryptosporidiosis from 1997 to 2015 were obtained from the national surveillance system. Retrospective space–time permutation was used to identify statistical clusters. Cluster data were compared to severe weather events in a national database. SaTScan analysis detected 38 statistically significant cryptosporidiosis clusters. Around a third (34.2%, 13/38) of these clusters showed temporal and spatial alignment with severe weather events. Of these, nearly half (46.2%, 6/13) occurred in the spring. Only five (38%, 5/13) of these clusters corresponded to a previously reported cryptosporidiosis outbreak. This study provides additional evidence that severe weather events may contribute to the development of some cryptosporidiosis clusters. Further research on this association is needed as rainfall intensity is projected to rise in NZ due to climate change. The findings also provide further arguments for upgrading the quality of drinking water sources to minimize contamination with pathogens from runoff from livestock agriculture.

OBJECTIVES/GOALS: Our study explores the dose-related effects of THC on cardiovascular measures, self-reported effects, balance, and cognitive function among older adults. We also evaluate the acceptability and feasibility of study procedures, to inform future study designs employing this population. METHODS/STUDY POPULATION: Using a within-subject, double-blind, placebo-controlled design and standard behavioral pharmacology methods, reasonably healthy male and female adults aged 55-70 years undergo an eligibility screening, followed by a mock session and 3 experimental sessions (>7 days apart). During experimental sessions, participants are administered cannabis-infused brownies with varying THC doses. Prior to and at multiple intervals post- consumption, subjects complete assessments including self reports and observer ratings, psychomotor and cognitive performance measures, and vital signs. Follow-up interviews regarding the experience will be conducted one day after each session. RESULTS/ANTICIPATED RESULTS: We anticipate our results to mirror those of previously reported studies conducted in adults under 45 years old in that a dose-response relationship exists for subjective drug effects and vital signs with the caveat that this relationship may be exacerbated in our population. We additionally anticipate findings that indicate THC impairs balance and coordination, potentially increasing the risk of falls and accidents among this population, and cognitive function, affecting attention, memory, and executive functions. Feedback provided during the follow-up interviews will help refine procedures for future studies, ensuring that the methodology is acceptable and feasible for this population. DISCUSSION/SIGNIFICANCE: Prior work demonstrates the safety and efficacy of THC in conditions common among older adults, however, no conclusive data regarding tolerability and safety in this population exists. The presented work is vital groundwork for future research on THC as a potential therapeutic for older adults.

Hollow spherical particles of aluminosilicate having diameters of 80 to 100 Å and high electric charge were synthesized by heating solutions containing Si and Al concentrations of about 2 mM (Si/Al molar ratio = 1.0–1.2; pH = 9.0) at 95°–100°C for 7 days. Electron microscopy, X-ray powder diffraction, and infrared spectroscopy suggested that the walls of the spherical particles consisted of monolayer aluminosilicate, most probably having a 1:1 layer structure. Chemical analysis supported this supposition but indicated modifications as shown in the formula (Si1.85Alo0.62)IV(Al1.38)VI(OH)4.10O4.96Na0.62, compared with (Si2)lv(Al2)VI(OH)4O5 for an ideal 1:1 layer silicate. High-resolution 29Si and 27A1 nuclear magnetic resonance spectroscopy indicated the substitution of Al for Si in the tetrahedral sheet, the presence of A1IV and A1VI, and the presence of Si bonded through oxygen to three Al atoms and one H. A natural counterpart of the synthesized aluminosilicate may be a precursor of halloysites formed by weathering of volcanic ash and pumice and have a close structural relation with allophane and imogolite

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

Experimental data on structure formation in highly concentrated aqueous dispersions of kaolinite were analyzed using rheological models. The physicochemical properties of the clay mineral surface were studied during heating at a range of temperatures, and correlation of acid-base properties with physicomechanical characteristics of the spatial structures formed during heating was obtained. It was shown that interparticle interactions and plastic yield mechanisms under load are dependent upon interfacial phenomena. A method for estimating optimal structural parameters was developed for semidry dispersions, enabling regulation of physicochemical and mechanical properties of ceramic mixtures during processing.

By focusing on peace, Glowacki provides a fresh perspective on warfare. Why did humans evolve peace? Other animals aggregate peacefully when resources are not economically defendable. The human capacity for peace may arise from two key factors: Multilevel societies and psychology shaped by within-group exchanges, which may have begun when tools enabled hominins to extract foods, including tubers and roots.

The adsorption of 13C-labeled benzene on imogolite has been studied on samples which had been evacuated and then heated to remove water below their decomposition point. After adsorption of labeled benzene, the samples were studied by nuclear magnetic resonance using non-spinning techniques. The results show that benzene can occupy more than one pore type and that water does not displace benzene from the intra-tube pores at atmospheric pressure. A further finding is that there are at least two types of adsorbed benzene in so called inter-tube pores, one of which is more rigidly held than that in intratube pores. The presence of disordered materials at the edge of pores could also play a role in altering the pore mouth thereby creating new types of pores. Moreover, where two tubes do not pack properly, space might be created where an adsorbed molecule may bind more tightly than expected in a conventional pore.

Reducing the environmental footprint of cement is an absolute necessity to meet the commitments of COP26 and to limit global warming to + 1.5°C compared to the pre-industrial level. In this context, particular interest has developed in recent years in the use of calcined clays as supplementary cementitious materials (SCMs). Due to their high reactivity, large reserves and homogeneous distribution on the earth's surface, calcined clays represent a viable alternative to conventional SCMs. Clay minerals are highly variable and numerous, each with their own characteristics. As a result, not all of them have potential for use as SCMs. The present paper investigated the use of palygorskite (a clay that has been relatively poorly studied) as an SCM. Two commercial palygorskites of different grades were selected and their calcination was studied by X-ray diffraction and pozzolanic activity tests. Blended cements incorporating 20% of each calcined palygorskite were prepared and the mechanical performance and resistivity of the mortars measured. The results show that the optimum calcination temperature is 800°C (allowing complete amorphization of the clay fraction and the highest pozzolanic reactivity) for both clays. Mortars made with 80% ordinary Portland cement (OPC) blended with 20% of 800°C calcined palygorskite allowed a significant increase in compressive strength and electrical resistivity compared to the reference (100% OPC). The clay sample with palygorskite as the dominant mineral exhibited the greatest pozzolanic reactivity and mechanical performance in cementitious systems, confirming that palygorskite is a clay mineral with a significant potential for a use as a SCM. The second sample with smaller palygorskite content also allowed a significant increase in mechanical performance. This demonstrated that it is not necessary to use high-purity samples and enhances the value of this type of material.

Alzheimer’s disease (AD) is a neurodegenerative disorder that accounts for 60%–70% of patients with dementia, and it is estimated that over one million Canadians will be living with dementia by 2030. Disease-modifying therapies (DMTs) targeting the underlying pathophysiology of AD are currently in development. Several models have demonstrated that the potential arrival of Alzheimer’s DMTs will most likely overwhelm the already-constrained Canadian healthcare system. Canada does not have a strategy to address the extensive requirements of using DMTs, including providing an early diagnosis of AD, confirming DMT eligibility via amyloid biomarkers, and conducting ongoing treatment monitoring. Thus, a multidisciplinary group of experts involved in AD care in Canada gathered to review (1) the current barriers to diagnosis and management of AD; (2) how existing clinic models, including those used in multiple sclerosis (MS), could be applied to address key barriers in AD; and (3) how to design and implement optimal care pathways in the future. The actions outlined in this review will help clinicians and healthcare systems improve readiness to integrate the use of disease-modifying therapies in Alzheimer’s disease, if such therapies are approved in Canada.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

Remote sensing survey in southern Jordan has identified at least three Roman temporary camps that indicate a probable undocumented military campaign into what is today Saudi Arabia, and which we conjecture is linked to the Roman annexation of the Nabataean kingdom in AD 106.

OBJECTIVES/GOALS: As hospitals across the nation respond to the need to address community violence, there is a dearth of Hospital-based Violence Intervention Programs (HVIPs) in the South despite having disproportionate rates. This research aims to identify key factors and strategies for implementation of an HVIP among rural patient populations in a southern state. METHODS/STUDY POPULATION: Semi-structured interviews will be conducted with medical providers, social service organizations, and patients transferred from four high-risk rural areas in Arkansas. Data will be analyzed using Framework Analysis, a rapid analysis approach involving framework development, code application, impactful statement identification, and content analysis. Evidence- Based Quality Improvement (EBQI), a group consensus making process, will be conducted to identify key implementation strategies and factors to adapt based interview findings. Priority areas for adaptation will be identified via systematic rating. The EBQI team, including researchers and key rural stakeholders will engage in a series of discussion, vote on final strategies, and develop a guide for future HVIP implementation and pilot testing. RESULTS/ANTICIPATED RESULTS: Findings from this study will result in a prioritized list of barriers and facilitators across sample groups. Factors will be rated by level of importance. Cluster maps will display the relationships among factors. Go and no-go zones will be identified based on importance and feasibility. Implementation strategies will be mapped to barriers and facilitators. DISCUSSION/SIGNIFICANCE: The findings will result in a culturally and geographically relevant HVIP model and package of implementation strategies to test in future hybrid trials (feasibility pilot & multi-site RCT); and shape the future of violence prevention efforts in healthcare settings across the rural South.

OBJECTIVES/GOALS: The rates of computational phenotyping algorithm reuse across health systems are low, leading to a proliferation of algorithms for the same trait. We propose a framework for reusing computational phenotyping algorithms and describe the real-world deployment of this framework for the development of the Colorado Diabetes EHR Research Repository. METHODS/STUDY POPULATION: The novel phenotype reuse framework consists of 4 steps: select algorithms that are appropriate for reuse by assessing whether they are fit for purpose; extend the algorithm to account for changes in data and care practice standards; localize the algorithm to use local database standards and terminologies; optimize the algorithm by applying a data driven approach to achieve the desired local performance. To identify individuals with type 1 diabetes (T1D) or type 2 diabetes (T2D), we selected and implemented T2D algorithms in a cohort of adults with any diabetes or pre-diabetes related diagnosis code, medication, or abnormal glucose-related laboratory test in the clinical data warehouse for UCHealth and the University of Colorado. RESULTS/ANTICIPATED RESULTS: We included a total of 926,290 patients who were identified by initial filters. Patients were more likely to be female (53%), identify as non-Hispanic white (69%) and had a median age of 58 years (IQR: 41, 70). Implementation, extension, localization, & optimization through iterative chart review prioritized high sensitivity for all-cause diabetes and high specificity for T1D and T2D. Of the original cohort, 252,946 (27%) were identified by the all-cause diabetes algorithm. Of these 11,688 were identified as T1D and 135,588 as T2D. After optimization the all-cause diabetes algorithm had 88% sensitivity, 90% specificity, 74% positive predictive value (PPV), and 96% negative predictive value (NPV). Our algorithms for T1D and T2D had high specificity (100% and 99%, respectively) and PPV (100 and 96% respectively). DISCUSSION/SIGNIFICANCE: Developing computational phenotyping algorithms is expensive and time consuming, yet algorithm reuse is low due to a lack of practical approaches for reusing algorithms. We demonstrate application of a novel framework for algorithm reuse, yielding good alignment of algorithm performance with study goals for identifying individuals with diabetes.